Abstract:
RATIONALE:Little is known about human club cells, dome-shaped cells with dense cytoplasmic granules and microvilli that represent the major secretory cells of the human small airways (at least sixth-generation bronchi). OBJECTIVES:To define the ontogeny and biology of the human small airway epithelium club cell. METHODS:The small airway epithelium was sampled from the normal human lung by bronchoscopy and brushing. Single-cell transcriptome analysis and air-liquid interface culture were used to assess club cell ontogeny and biology. MEASUREMENTS AND MAIN RESULTS:We identified the club cell population by unbiased clustering using single-cell transcriptome sequencing. Principal component gradient analysis uncovered an ontologic link between KRT5 (keratin 5)+ basal cells and SCGB1A1 (secretoglobin family 1A member 1)+ club cells, a hypothesis verified by demonstrating in vitro that a pure population of human KRT5+ SCGB1A1- small airway epithelial basal cells differentiate into SCGB1A1+KRT5- club cells on air-liquid interface culture. Using SCGB1A1 as the marker of club cells, the single-cell analysis identified novel roles for these cells in host defense, xenobiotic metabolism, antiprotease, physical barrier function, monogenic lung disorders, and receptors for human viruses. CONCLUSIONS:These observations provide novel insights into the molecular phenotype and biologic functions of the human club cell population and identify basal cells as the human progenitor cells for club cells.
journal_name
Am J Respir Crit Care Medauthors
Zuo WL,Shenoy SA,Li S,O'Beirne SL,Strulovici-Barel Y,Leopold PL,Wang G,Staudt MR,Walters MS,Mason C,Kaner RJ,Mezey JG,Crystal RGdoi
10.1164/rccm.201710-2107OCsubject
Has Abstractpub_date
2018-12-01 00:00:00pages
1375-1388issue
11eissn
1073-449Xissn
1535-4970journal_volume
198pub_type
杂志文章abstract:RATIONALE:Patent foramen ovale (PFO) may be disadvantageous in chronic obstructive pulmonary disease (COPD). It is unknown whether right-to-left shunting through PFO increases during exercise impairing exercise performance. OBJECTIVES:To determine whether (1) PFO prevalence is greater in hypoxemic versus less hypoxemi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201309-1618OC
更新日期:2014-03-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a generally fatal disorder with a reported median survival of 3 to 6 yr. This has been based on relatively few studies with diagnoses inconsistently confirmed by adequate lung biopsy. Retrospective analysis of 104 patients with IPF who had open lung biopsy (OLB) at Mayo Medical C...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.1.9704130
更新日期:1998-01-01 00:00:00
abstract:RATIONALE:S. aureus is the most common respiratory pathogen isolated from patients with cystic fibrosis (CF) in the US. While modes of acquisition and genetic adaptation have been described for Pseudomonas aeruginosa, resulting in improved diagnosis and treatment, these features remain more poorly defined for S. aureus...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.202003-0735OC
更新日期:2020-12-09 00:00:00
abstract:RATIONALE:Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed duration of antiviral prophylaxis despite the associated cost and...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201504-0733OC
更新日期:2016-01-01 00:00:00
abstract:RATIONALE:Although intermittent, three-times-weekly therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium complex (MAC) lung disease, supporting data are limited. OBJECTIVES:To evaluate the clinical efficacy of intermittent therapy compared with daily therapy for no...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201408-1545OC
更新日期:2015-01-01 00:00:00
abstract:RATIONALE:Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition with unclear pathogenesis. Two competing theories of the pathogenesis of EIB differ regarding the inflammatory basis of this condition. OBJECTIVES:Our goals were to establish whether epithelial cell and mast cell activation with relea...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/rccm.200412-1667OC
更新日期:2005-09-15 00:00:00
abstract::It is generally accepted that tuberculosis results from a single infection with a single Mycobacterium tuberculosis strain. Such infections are thought to confer protective immunity against exogenous reinfection. In this study, a novel polymerase chain reaction method was developed to specifically identify M. tubercul...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200305-714OC
更新日期:2004-03-01 00:00:00
abstract:RATIONALE:In San Francisco, 70% of the tuberculosis cases occur among foreign-born persons, mainly from China, the Philippines, and Mexico. We postulate that there are differences in the characteristics and risk factors for tuberculosis among these populations. OBJECTIVES:To determine the clinical, epidemiological and...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201212-2239OC
更新日期:2013-05-01 00:00:00
abstract::We investigated the source of intravascular fat in systemic organs (brain, heart, and kidney) after massive pulmonary fat embolism during cemented arthroplasty. We used a bilateral cemented arthroplasty (BCA) in anesthetized mongrel dogs that simulates a cemented total-hip replacement procedure. We hypothesized that d...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.5.7952570
更新日期:1994-11-01 00:00:00
abstract:RATIONALE:Surfactant protein D (SP-D), a 43-kD collectin, is synthesized and secreted by airway epithelia as a dodecamer formed by assembly of four trimeric subunits. We have previously shown that the quaternary structure of SP-D can be altered during inflammatory lung injury through its modification by S-nitrosylation...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201004-0654OC
更新日期:2011-04-01 00:00:00
abstract::Platelets are an important, albeit generally underappreciated, component of the inflammatory cascade. Platelets are known to contribute to inflammation in atherosclerosis, stroke, and asthma. They produce a large number of proinflammatory lipid mediators and cytokines, and play a vital role in recruitment of leukocyte...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.200508-1243PP
更新日期:2006-03-01 00:00:00
abstract::The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), have been associated with accelerated metabolism and protein turnover following exogenous administration in normal humans. We hypothesized that these inflammatory cytokines might contribute to the weight-losing proc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.2.8564110
更新日期:1996-02-01 00:00:00
abstract::Normative spirometric values were derived from 5,042 white (of mainly European ancestry) and black (of mainly African ancestry) men and women paper plant workers who are never-smokers, with no respiratory symptoms or diagnoses and no history of occupational exposure to fibrogenic dusts or irritant chemicals. This coho...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.2.7842200
更新日期:1995-02-01 00:00:00
abstract::The role of nutritional status in the prognosis of subjects with severe chronic obstructive pulmonary disease was studied in a cohort of Canadian men and women followed for 3 to 5 yr. A total of 348 subjects who were recruited for a study of negative pressure ventilation were evaluated for lung function and body weigh...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.3.8630580
更新日期:1996-03-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200909-1398OC
更新日期:2010-05-15 00:00:00
abstract:RATIONALE:The CD40 protein plays important roles in cell-mediated and humoral immune responses, especially in immunoglobulin class-switching to IgE. OBJECTIVES:We tested the association of CD40 polymorphisms with the risk of asthma and the level of serum IgE and investigated the functional effect of associated polymor...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200609-1286OC
更新日期:2007-04-15 00:00:00
abstract::Quality of life has been found to be impaired both in patients with asthma and in patients with allergic rhinitis, but the relative burden of these diseases has not been investigated. We analyzed answers to the SF-36 questionnaire from 850 subjects recruited in two French centers participating in the European Communit...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.4.9912033
更新日期:2000-10-01 00:00:00
abstract:RATIONALE:The activated leukocyte cell adhesion molecule (ALCAM) is a cluster of differentiation 6 ligand that is important for stabilizing the immunological synapse and inducing T-cell activation and proliferation. OBJECTIVES:In this study, we investigated the role of ALCAM in the development of inflammation in aller...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201703-0532OC
更新日期:2018-04-15 00:00:00
abstract::In addition to its central role in hemostasis, thrombin may play a role in inflammation and remodeling. To investigate the contribution of thrombin to allergic airway inflammation in asthma, we used an enzymatic assay to determine thrombin activity in bronchoalveolar lavage fluid obtained from 19 subjects with atopic ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200308-1156OC
更新日期:2004-02-01 00:00:00
abstract:RATIONALE:The molecular mechanisms underlying acute exacerbations of idiopathic pulmonary fibrosis (IPF) are poorly understood. We studied the global gene expression signature of acute exacerbations of IPF. OBJECTIVES:To understand the gene expression patterns of acute exacerbations of IPF. METHODS:RNA was extracted ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200810-1596OC
更新日期:2009-07-15 00:00:00
abstract::Although abnormalities of alveolar fibrin turnover have been reported to play a role in the development of idiopathic pulmonary fibrosis (IPF), the pathophysiological relevance remains unclear. We therefore investigated the localization of tissue factor (TF) and fibrin deposition in patients with IPF using immunohisto...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.2.9608094
更新日期:1997-08-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.200607-916OC
更新日期:2007-09-01 00:00:00
abstract::Clinicians are frequently faced with patients in whom the radiographic resolution of community-acquired pneumonia seems delayed. Previous studies of radiographic resolution of the disease have yielded conflicting results. We prospectively assessed the radiographic resolution of pneumonia in 81 non-immuno-compromised p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.149.3.8118630
更新日期:1994-03-01 00:00:00
abstract:RATIONALE:The acute respiratory distress syndrome is a significant cause of morbidity and mortality in critically ill patients. Angiopoietin-1 (Ang-1), a ligand for the endothelial Tie2 receptor, is an endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-en...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200609-1370OC
更新日期:2007-05-15 00:00:00
abstract:RATIONALE:Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children's phthalate exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examine...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201203-0398OC
更新日期:2012-11-01 00:00:00
abstract:RATIONALE:The effects of prenatal cigarette smoke (CS) exposure and hypoxemia on cardiorespiratory control have been investigated in full-term infants. However, few data are available in preterm infants, who form a particularly vulnerable population, with developmentally immature cardiorespiratory control. OBJECTIVES:...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200803-432OC
更新日期:2008-09-01 00:00:00
abstract::Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12-21.3 haploid deletion encompa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201002-0167CR
更新日期:2010-08-15 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.201405-0850OC
更新日期:2014-10-01 00:00:00
abstract::We investigated 116 Italian atopic families (560 individuals) for linkage with 13 DNA markers on chromosome 12. All the subjects were phenotyped for asthma, total serum IgE, bronchial hyperresponsiveness, skin-prick positivity to common aeroallergens, and atopy. A relative location map of the markers was prepared from...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.4.9909031
更新日期:2000-10-01 00:00:00
abstract:RATIONALE:Bronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
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更新日期:2017-10-01 00:00:00